JP2008073098A - Bioimplant - Google Patents
Bioimplant Download PDFInfo
- Publication number
- JP2008073098A JP2008073098A JP2006252933A JP2006252933A JP2008073098A JP 2008073098 A JP2008073098 A JP 2008073098A JP 2006252933 A JP2006252933 A JP 2006252933A JP 2006252933 A JP2006252933 A JP 2006252933A JP 2008073098 A JP2008073098 A JP 2008073098A
- Authority
- JP
- Japan
- Prior art keywords
- calcium phosphate
- antibacterial agent
- coating
- coating film
- crystallinity
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 238000000576 coating method Methods 0.000 claims abstract description 51
- 239000011248 coating agent Substances 0.000 claims abstract description 47
- 239000003242 anti bacterial agent Substances 0.000 claims abstract description 43
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 claims abstract description 42
- 239000001506 calcium phosphate Substances 0.000 claims abstract description 32
- 229910000389 calcium phosphate Inorganic materials 0.000 claims abstract description 31
- 235000011010 calcium phosphates Nutrition 0.000 claims abstract description 31
- 239000007943 implant Substances 0.000 claims abstract description 28
- 239000000463 material Substances 0.000 claims abstract description 13
- 230000003115 biocidal effect Effects 0.000 claims abstract description 9
- 229910052588 hydroxylapatite Inorganic materials 0.000 claims description 28
- XYJRXVWERLGGKC-UHFFFAOYSA-D pentacalcium;hydroxide;triphosphate Chemical compound [OH-].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O XYJRXVWERLGGKC-UHFFFAOYSA-D 0.000 claims description 28
- 230000008034 disappearance Effects 0.000 claims description 26
- 238000000034 method Methods 0.000 claims description 18
- 238000010828 elution Methods 0.000 claims description 17
- 239000010410 layer Substances 0.000 claims description 15
- 239000000203 mixture Substances 0.000 claims description 10
- 238000010438 heat treatment Methods 0.000 claims description 7
- 238000004544 sputter deposition Methods 0.000 claims description 7
- 238000010285 flame spraying Methods 0.000 claims description 6
- 239000011521 glass Substances 0.000 claims description 5
- 239000002241 glass-ceramic Substances 0.000 claims description 4
- 238000002156 mixing Methods 0.000 claims description 3
- 238000005240 physical vapour deposition Methods 0.000 claims description 3
- 238000007751 thermal spraying Methods 0.000 claims description 3
- 238000007737 ion beam deposition Methods 0.000 claims description 2
- 238000007733 ion plating Methods 0.000 claims description 2
- 150000002500 ions Chemical class 0.000 claims description 2
- 210000000281 joint capsule Anatomy 0.000 claims description 2
- 238000007750 plasma spraying Methods 0.000 claims description 2
- 239000002356 single layer Substances 0.000 claims description 2
- 238000003980 solgel method Methods 0.000 claims description 2
- 239000002344 surface layer Substances 0.000 claims description 2
- 239000004068 calcium phosphate ceramic Substances 0.000 claims 1
- 239000011247 coating layer Substances 0.000 abstract description 9
- 239000010408 film Substances 0.000 description 49
- 230000000844 anti-bacterial effect Effects 0.000 description 20
- 210000000988 bone and bone Anatomy 0.000 description 14
- 210000004394 hip joint Anatomy 0.000 description 11
- 239000010936 titanium Substances 0.000 description 9
- RTAQQCXQSZGOHL-UHFFFAOYSA-N Titanium Chemical compound [Ti] RTAQQCXQSZGOHL-UHFFFAOYSA-N 0.000 description 7
- 229940088710 antibiotic agent Drugs 0.000 description 7
- 229910052719 titanium Inorganic materials 0.000 description 7
- NDVLTYZPCACLMA-UHFFFAOYSA-N silver oxide Chemical compound [O-2].[Ag+].[Ag+] NDVLTYZPCACLMA-UHFFFAOYSA-N 0.000 description 6
- FOIXSVOLVBLSDH-UHFFFAOYSA-N Silver ion Chemical compound [Ag+] FOIXSVOLVBLSDH-UHFFFAOYSA-N 0.000 description 5
- 239000012888 bovine serum Substances 0.000 description 5
- 239000000758 substrate Substances 0.000 description 5
- 229910000684 Cobalt-chrome Inorganic materials 0.000 description 4
- 241000588724 Escherichia coli Species 0.000 description 4
- 241000191967 Staphylococcus aureus Species 0.000 description 4
- 229910045601 alloy Inorganic materials 0.000 description 4
- 239000000956 alloy Substances 0.000 description 4
- 229910052586 apatite Inorganic materials 0.000 description 4
- 210000001124 body fluid Anatomy 0.000 description 4
- 239000010839 body fluid Substances 0.000 description 4
- 239000010952 cobalt-chrome Substances 0.000 description 4
- 238000004090 dissolution Methods 0.000 description 4
- 208000015181 infectious disease Diseases 0.000 description 4
- VSIIXMUUUJUKCM-UHFFFAOYSA-D pentacalcium;fluoride;triphosphate Chemical compound [F-].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O VSIIXMUUUJUKCM-UHFFFAOYSA-D 0.000 description 4
- 238000011056 performance test Methods 0.000 description 4
- 241000894006 Bacteria Species 0.000 description 3
- 210000001503 joint Anatomy 0.000 description 3
- 230000002265 prevention Effects 0.000 description 3
- 229910052709 silver Inorganic materials 0.000 description 3
- 239000004332 silver Substances 0.000 description 3
- 229910001923 silver oxide Inorganic materials 0.000 description 3
- 238000005507 spraying Methods 0.000 description 3
- 238000001356 surgical procedure Methods 0.000 description 3
- 208000035473 Communicable disease Diseases 0.000 description 2
- WAIPAZQMEIHHTJ-UHFFFAOYSA-N [Cr].[Co] Chemical compound [Cr].[Co] WAIPAZQMEIHHTJ-UHFFFAOYSA-N 0.000 description 2
- FUWUEFKEXZQKKA-UHFFFAOYSA-N beta-thujaplicin Chemical compound CC(C)C=1C=CC=C(O)C(=O)C=1 FUWUEFKEXZQKKA-UHFFFAOYSA-N 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 2
- 238000007922 dissolution test Methods 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 210000001624 hip Anatomy 0.000 description 2
- 238000005470 impregnation Methods 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 230000000399 orthopedic effect Effects 0.000 description 2
- 201000008482 osteoarthritis Diseases 0.000 description 2
- 239000002953 phosphate buffered saline Substances 0.000 description 2
- 239000002504 physiological saline solution Substances 0.000 description 2
- 238000010837 poor prognosis Methods 0.000 description 2
- -1 silver ions Chemical class 0.000 description 2
- 208000035143 Bacterial infection Diseases 0.000 description 1
- 208000020084 Bone disease Diseases 0.000 description 1
- 229910014497 Ca10(PO4)6(OH)2 Inorganic materials 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- JPVYNHNXODAKFH-UHFFFAOYSA-N Cu2+ Chemical compound [Cu+2] JPVYNHNXODAKFH-UHFFFAOYSA-N 0.000 description 1
- 206010067268 Post procedural infection Diseases 0.000 description 1
- BLRPTPMANUNPDV-UHFFFAOYSA-N Silane Chemical compound [SiH4] BLRPTPMANUNPDV-UHFFFAOYSA-N 0.000 description 1
- BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 description 1
- 206010061363 Skeletal injury Diseases 0.000 description 1
- 229910001069 Ti alloy Inorganic materials 0.000 description 1
- 108010059993 Vancomycin Proteins 0.000 description 1
- PTFCDOFLOPIGGS-UHFFFAOYSA-N Zinc dication Chemical compound [Zn+2] PTFCDOFLOPIGGS-UHFFFAOYSA-N 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- TUFYVOCKVJOUIR-UHFFFAOYSA-N alpha-Thujaplicin Natural products CC(C)C=1C=CC=CC(=O)C=1O TUFYVOCKVJOUIR-UHFFFAOYSA-N 0.000 description 1
- 238000002266 amputation Methods 0.000 description 1
- 239000012227 artificial bone substitute Substances 0.000 description 1
- 208000022362 bacterial infectious disease Diseases 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 229960001716 benzalkonium Drugs 0.000 description 1
- CYDRXTMLKJDRQH-UHFFFAOYSA-N benzododecinium Chemical compound CCCCCCCCCCCC[N+](C)(C)CC1=CC=CC=C1 CYDRXTMLKJDRQH-UHFFFAOYSA-N 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 239000012620 biological material Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000000316 bone substitute Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 239000000919 ceramic Substances 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 229910001431 copper ion Inorganic materials 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 239000011222 crystalline ceramic Substances 0.000 description 1
- 229910002106 crystalline ceramic Inorganic materials 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 238000010335 hydrothermal treatment Methods 0.000 description 1
- 238000002513 implantation Methods 0.000 description 1
- 238000011542 limb amputation Methods 0.000 description 1
- 229910021645 metal ion Inorganic materials 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 230000001376 precipitating effect Effects 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 229910000077 silane Inorganic materials 0.000 description 1
- GBNXLQPMFAUCOI-UHFFFAOYSA-H tetracalcium;oxygen(2-);diphosphate Chemical compound [O-2].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O GBNXLQPMFAUCOI-UHFFFAOYSA-H 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000007669 thermal treatment Methods 0.000 description 1
- 239000010409 thin film Substances 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 229910000391 tricalcium phosphate Inorganic materials 0.000 description 1
- 235000019731 tricalcium phosphate Nutrition 0.000 description 1
- 229940078499 tricalcium phosphate Drugs 0.000 description 1
- 229960003165 vancomycin Drugs 0.000 description 1
- MYPYJXKWCTUITO-LYRMYLQWSA-N vancomycin Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC1=C2C=C3C=C1OC1=CC=C(C=C1Cl)[C@@H](O)[C@H](C(N[C@@H](CC(N)=O)C(=O)N[C@H]3C(=O)N[C@H]1C(=O)N[C@H](C(N[C@@H](C3=CC(O)=CC(O)=C3C=3C(O)=CC=C1C=3)C(O)=O)=O)[C@H](O)C1=CC=C(C(=C1)Cl)O2)=O)NC(=O)[C@@H](CC(C)C)NC)[C@H]1C[C@](C)(N)[C@H](O)[C@H](C)O1 MYPYJXKWCTUITO-LYRMYLQWSA-N 0.000 description 1
- MYPYJXKWCTUITO-UHFFFAOYSA-N vancomycin Natural products O1C(C(=C2)Cl)=CC=C2C(O)C(C(NC(C2=CC(O)=CC(O)=C2C=2C(O)=CC=C3C=2)C(O)=O)=O)NC(=O)C3NC(=O)C2NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(CC(C)C)NC)C(O)C(C=C3Cl)=CC=C3OC3=CC2=CC1=C3OC1OC(CO)C(O)C(O)C1OC1CC(C)(N)C(O)C(C)O1 MYPYJXKWCTUITO-UHFFFAOYSA-N 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 229930007845 β-thujaplicin Natural products 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
- A61F2/02—Prostheses implantable into the body
- A61F2/30—Joints
- A61F2/32—Joints for the hip
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
- A61F2/02—Prostheses implantable into the body
- A61F2/30—Joints
- A61F2002/30001—Additional features of subject-matter classified in A61F2/28, A61F2/30 and subgroups thereof
- A61F2002/30667—Features concerning an interaction with the environment or a particular use of the prosthesis
- A61F2002/30677—Means for introducing or releasing pharmaceutical products, e.g. antibiotics, into the body
Landscapes
- Health & Medical Sciences (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Cardiology (AREA)
- Oral & Maxillofacial Surgery (AREA)
- Transplantation (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Heart & Thoracic Surgery (AREA)
- Vascular Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Materials For Medical Uses (AREA)
- Prostheses (AREA)
Abstract
Description
本発明は、生体インプラントの消失性コーティング、更に詳細には、抗菌剤又は抗菌薬を含有させた消失性コーティング被覆生体インプラントに関する。 The present invention relates to an evanescent coating for a bioimplant, and more particularly, to an evanescent coating-coated bioimplant containing an antibacterial agent or an antibacterial agent.
骨傷害／疾病双方の治療に生体インプラント装置を使用することは、活動的な人口及び老人人口が増加すると共に絶えず拡大している。骨破砕及び骨除去のための骨代替物の使用又は脆弱化した骨のためのサポートの使用には、人工骨代替物が、生来骨とともに、強い関節又は骨を形成して、構造の完全性を保障することを必要とする。骨は隣接構造中へ、特に隣接構造が、多孔質であり、骨に匹敵する場合に、その中へ成長していくことができるけれども、骨が、多孔質構造中へ成長していけるだけではなく、中に成長した生来の骨と生体インプラント装置との間の強い接着を可能にする形での結合があらねばならないとされる。 The use of bioimplant devices for the treatment of both bone injuries / diseases is constantly expanding as the active and aging populations increase. For the use of bone substitutes for bone crushing and bone removal or the use of supports for weakened bones, artificial bone substitutes, together with native bones, form strong joints or bones to ensure structural integrity. You need to ensure. Bone can enter into adjacent structures, especially if the adjacent structure is porous and comparable to bone, but it can only grow into a porous structure. Rather, there must be a bond in a form that allows strong adhesion between the native bone grown therein and the bioimplant device.
生体インプラントの骨への固着のために重要な要件は、骨がインプラント表面へ及び／又は中へ成長することである。多数の研究により、コバルト−クロム（Ｃｏ−Ｃｒ）及びチタン（Ｔｉ）−合金インプラント上のリン酸カルシウムコーティング、例えば生物的アパタイトは、合金だけの裸表面の時より遥かに迅速に骨付着を促進することが示される。生物的アパタイトＣａ10（ＰＯ4）6（ＯＨ）2は、ヒトの骨および歯起源の主要化合物の1つである。この合成形の、ヒドロキシアパタイト（ＨＡ）は、天然産アパタイトに非常に類似しており、歯科及び整形外科インプラントでＨＡを使用する研究へ導かれた。ＨＡ又は他の結晶性リン酸カルシウムを用いる被覆により、移植後、周囲の骨及び組織と容易に一体化するインプラントが製造される。 An important requirement for the fixation of the bioimplant to the bone is that the bone grows on and / or into the implant surface. Numerous studies have shown that calcium phosphate coatings, such as biological apatite, on cobalt-chromium (Co-Cr) and titanium (Ti) -alloy implants promote bone attachment much more quickly than when the bare surface is alloy-only. Is shown. Biological apatite Ca 10 (PO 4 ) 6 (OH) 2 is one of the major compounds of human bone and dental origin. This synthetic form, hydroxyapatite (HA), is very similar to naturally occurring apatite and has led to studies using HA in dental and orthopedic implants. Coating with HA or other crystalline calcium phosphate produces an implant that readily integrates with the surrounding bone and tissue after implantation.
しかしながら、人工関節の手術後に細菌が関節内で増殖し、感染症を起こすと、感染した人工関節を手術で抜去して抗生物質による感染治療（数週間乃至数ヶ月）し、人工関節を再置換することになる。また、予後不良の場合は、関節固定や手足の切断に至るなど回復しがたい問題となる。 However, if bacteria grow in the joint after an artificial joint surgery and an infection occurs, the infected artificial joint is removed by surgery and treated with antibiotics (weeks to months), and the artificial joint is replaced again. Will do. In addition, in the case of poor prognosis, it becomes a problem that is difficult to recover, such as joint fixation and limb amputation.
そこで、インプラントの表面にハイドロキシアパタイトを沈殿させ、それを乾燥させることにより抗生物質などの含浸に適した、結晶性が高く比表面積が大きなハイドロキシアパタイト層をコーティングする方法、そのコーティング層に抗生物質などを含浸させる治療剤含浸インプラントが提案されている（特許文献１）。
上記結晶性ヒドロキシアパタイトは、抗生物質の含浸には適するものの、被膜の気孔径、気孔率が均一であるため、希望する速度で薬剤を徐放させることが困難であり、薬剤は一定速度で一気に溶出する傾向にある。このように抗生物質が溶出してしまうと抗菌性能が終了して有効期間が制御できないという問題がある。また、水に溶解する天然系、有機系抗菌剤は結晶性ヒドロキシアパタイトのコーティング層の構造によって保持され、そこからの溶出により抗菌性能を発揮できるが、これらの抗菌性能は一般に無機系抗菌剤に比して低く、抗生物質同様に耐性菌が発生しやすいので、生体インプラントの感染症防止には無機系抗菌剤の使用が望まれる。しかしながら、非溶解性であるため、結晶性ヒドロキシアパタイト膜からの溶出現象を利用するのが困難であるという問題がある。 Although the above crystalline hydroxyapatite is suitable for impregnation with antibiotics, since the pore diameter and porosity of the film are uniform, it is difficult to release the drug slowly at a desired rate. It tends to elute. Thus, when antibiotics elute, there exists a problem that an antibacterial performance is complete | finished and an effective period cannot be controlled. In addition, natural and organic antibacterial agents that dissolve in water are retained by the structure of the crystalline hydroxyapatite coating layer, and can exhibit antibacterial performance by elution from the coating layer. Compared with antibiotics, resistant bacteria are likely to be generated as in the case of antibiotics. Therefore, it is desired to use an inorganic antibacterial agent for the prevention of infectious diseases of living implants. However, since it is insoluble, there is a problem that it is difficult to use the elution phenomenon from the crystalline hydroxyapatite film.
本発明者らは、上記結晶性ヒドロキシアパタイトのコーティング層の結晶度を９０％以下に調整するとコーティング層の体内での消失性が得られ、その結晶度および組成により消失速度が制御できるだけでなく、膜厚により消失期間を調整できることを見出した。
本発明は、かかる知見に基づいて完成されたものであって、その要旨とするところは、インプラントの所定部位に結晶度が９０％以下のリン酸カルシウム系材料からなる消失性コーティング膜を形成し、抗菌剤又は抗菌薬を含有させてなることを特徴とする生体インプラントにある。
The inventors of the present invention can adjust the crystallinity of the coating layer of the crystalline hydroxyapatite to 90% or less to obtain the disappearance in the body of the coating layer, and not only can the disappearance rate be controlled by the crystallinity and composition, It has been found that the disappearance period can be adjusted by the film thickness.
The present invention has been completed based on such knowledge, and the gist of the present invention is that an anti-bacterial coating film made of a calcium phosphate-based material having a crystallinity of 90% or less is formed at a predetermined site of an implant, and is antibacterial. A biological implant characterized by containing an agent or an antibacterial agent.
本発明によれば、インプラントの所定部位に消失性コーティング膜を形成し、抗菌剤又は抗菌薬を含有させるので、膜の消失速度により抗菌剤の放出速度をコントロールすることができる。膜の消失速度は膜の結晶度および膜の組成に依存し、膜の消失期間は消失速度と膜厚に依存するので、これらを調整して最適な抗菌環境を所定の部所に、所定期間形成することができる。しかも膜の消失性を利用して抗菌剤を放出するので、非溶解性の無機系抗菌剤を使用することができるようになる。したがって、術後の感染症を防止する有効な態様を要望に応じて構成することができ、人工関節の抜去、再置換、予後不良時の関節固定や手足の切断という最悪の事態を避けることができる。 According to the present invention, since the vanishing coating film is formed at a predetermined site of the implant and contains the antibacterial agent or the antibacterial agent, the release rate of the antibacterial agent can be controlled by the disappearance rate of the film. The disappearance rate of the film depends on the crystallinity of the film and the composition of the film, and the disappearance period of the film depends on the disappearance rate and the film thickness. Can be formed. In addition, since the antibacterial agent is released utilizing the disappearance of the film, an insoluble inorganic antibacterial agent can be used. Therefore, an effective mode for preventing postoperative infection can be configured on demand, avoiding the worst situation of extraction, replacement, joint fixation or amputation in case of poor prognosis it can.
本発明の要旨とするところは、インプラントの所定部位に結晶度が９０％以下のリン酸カルシウム系材料からなる消失性コーティング膜を形成し、抗菌剤又は抗菌薬を含有させてなる生体インプラントにあるが、本発明において使用されるリン酸カルシウム系材料としては、ハイドロキシアパタイト（ＨＡ）、第３リン酸カルシウム（ＴＣＰ）、第４リン酸カルシウム（ＴｅＣＰ）を含むリン酸カルシウム系セラミックス、リン酸カルシウム系ガラス、およびリン酸カルシウム系ガラスセラミックスから１種又は２種以上の混合物が選ばれる。
リン酸カルシウム系材料組成は本発明のコーティング膜の消失速度を制御する１因子であり、難溶解性のリン酸カルシウムである結晶性ハイドロキシアパタイト（ＨＡ）、溶解性のリン酸カルシウムである第３リン酸カルシウム（ＴＣＰ）、第４リン酸カルシウム（ＴｅＣＰ）、リン酸カルシウム系ガラス、およびリン酸カルシウム系ガラスセラミックスを適宜比率で混成することにより消失速度を調整することができる。
例えば、体液中でのハイドロキシアパタイトの消失速度を１とすると、α−ＴＣＰの消失速度は１０、β−ＴＣＰの消失速度は３程度である。したがって、リン酸カルシウム系材料組成を調整することにより消失速度が調整できることが理解できる。
因みに、体液中でのハイドロキシアパタイトの消失速度を１としたときの消失速度を例示すると次の通りである。
消失速度（対ＨＡ＝１）
α−ＴＣＰ １０
β−ＴＣＰ ３
第４リン酸カルシウム（ＯＣＰ） ２
リン酸カルシウム系ガラス ９
リン酸カルシウム系ガラスセラミックス ５
The gist of the present invention lies in a biological implant formed with an antibacterial agent or an antibacterial agent by forming an extinguishing coating film made of a calcium phosphate material having a crystallinity of 90% or less at a predetermined site of the implant. As the calcium phosphate-based material used in the present invention, one or more kinds of calcium phosphate-based ceramics including calcium apatite (HA), tertiary calcium phosphate (TCP), and fourth calcium phosphate (TeCP), calcium phosphate-based glass, and calcium phosphate-based glass ceramics are used. A mixture of two or more is selected.
The calcium phosphate-based material composition is one factor that controls the disappearance rate of the coating film of the present invention. Crystalline hydroxyapatite (HA), which is a poorly soluble calcium phosphate, tricalcium phosphate (TCP), which is a soluble calcium phosphate, The disappearance rate can be adjusted by mixing calcium phosphate (TeCP), calcium phosphate glass, and calcium phosphate glass ceramics in an appropriate ratio.
For example, assuming that the disappearance rate of hydroxyapatite in body fluid is 1, the disappearance rate of α-TCP is 10, and the disappearance rate of β-TCP is about 3. Therefore, it can be understood that the disappearance rate can be adjusted by adjusting the calcium phosphate material composition.
Incidentally, the disappearance rate when the disappearance rate of hydroxyapatite in the body fluid is assumed to be 1 is as follows.
Vanishing speed (vs HA = 1)
α-TCP 10
β-TCP 3
Tetracalcium phosphate (OCP) 2
Calcium phosphate glass 9
Calcium phosphate glass ceramics 5
膜形成方法が、フレーム溶射、高速フレーム溶射、プラズマ溶射などの溶射法又はスパッタリング、イオンプレーテイング、イオンビーム蒸着、イオンミキシング法などの物理的蒸着法或いはゾルゲル法などの湿式コーティング法が選択されるが、膜生成方法は生成膜の結晶度に関連する。即ち、上記溶射法や物理的蒸着法でリン酸カルシウム系材料をコーティングした場合、通常非晶質層が形成される。これらの非晶質層に対して真空熱処理、レーザ熱処理、水熱処理などで熱的処理を加えることによりＨＡ等の結晶層を析出させることができる。リン酸カルシウム系の非晶質層は体液中で最も溶出しやすい状態であるが、熱処理などで結晶度を調節することによって結晶性のセラミックスの場合よりも広く溶出速度を制御することができる。
例えば、スパッタリングは膜厚が薄い膜形成方法に適し、結晶度１００％のＨＡをスパッタリングすることで、結晶度９０％以下の消失性コーティング膜を０．１以上５μｍまでの膜厚で形成することができる。かかる膜は１ヶ月以内の短期消失性コーティング膜として有効な性能を備えることになる。
他方、溶射方法は５μｍ以上１００μｍまでの厚いコーティング膜を形成するのに適しており、結晶度１００％のＨＡを溶射すると通常結晶度１０％程度のコーティング膜が形成される。この場合、２０μｍで６ヶ月消失、４０μｍで１カ年消失のコーティング膜を形成できる。一方、熱処理を施すことによって結晶度を上げることができ、消失速度を調整することができる。このコーティング層の場合、６５０℃、３時間の熱処理で結晶度を６０％まで上げることができる。しかしながら熱処理条件を上げても結晶度は９０％以上にはならない。
As the film forming method, a thermal spraying method such as flame spraying, high-speed flame spraying, or plasma spraying, or a physical vapor deposition method such as sputtering, ion plating, ion beam deposition, or ion mixing method, or a wet coating method such as a sol-gel method is selected. However, the film generation method is related to the crystallinity of the generated film. That is, when the calcium phosphate material is coated by the above spraying method or physical vapor deposition method, an amorphous layer is usually formed. A crystal layer such as HA can be deposited by applying thermal treatment to these amorphous layers by vacuum heat treatment, laser heat treatment, hydrothermal treatment, or the like. The calcium phosphate-based amorphous layer is most easily eluted in body fluids, but the dissolution rate can be controlled more widely than in the case of crystalline ceramics by adjusting the crystallinity by heat treatment or the like.
For example, sputtering is suitable for a method of forming a thin film. By sputtering HA having a crystallinity of 100%, an extinguishing coating film having a crystallinity of 90% or less can be formed to a thickness of 0.1 to 5 μm. Can do. Such a film has an effective performance as a short-term disappearing coating film within one month.
On the other hand, the thermal spraying method is suitable for forming a thick coating film having a thickness of 5 μm to 100 μm. When HA having a crystallinity of 100% is sprayed, a coating film having a crystallinity of approximately 10% is usually formed. In this case, it is possible to form a coating film that disappears for 6 months at 20 μm and disappears for one year at 40 μm. On the other hand, the crystallinity can be increased by heat treatment, and the disappearance rate can be adjusted. In the case of this coating layer, the crystallinity can be increased to 60% by heat treatment at 650 ° C. for 3 hours. However, even if the heat treatment conditions are increased, the crystallinity does not exceed 90%.
したがって、コーティング膜消失期間をリン酸カルシウム系材料で形成したコーティング膜の結晶度、組成、および膜厚により調整し、１週間から２４ヶ月に設定することができる。
消失期間 材料組成 膜形成方法 膜厚（μｍ） 結晶度
１週間 ＨＡ スパッタリング ０．５ １０％
３週間 ＨＡ スパッタリング ２ １０％
６ヶ月 ＨＡ 溶射法 ２０ １０％
１２ヶ月 ＨＡ 溶射法 ４０ １０％
Therefore, the coating film disappearance period can be adjusted by the crystallinity, composition, and film thickness of the coating film formed of the calcium phosphate material, and can be set from 1 week to 24 months.
Disappearance period Material composition Film formation method Film thickness (μm) Crystallinity 1 week HA Sputtering 0.5 10%
3 weeks HA sputtering 2 10%
6 months HA spraying method 20 10%
12 months HA spraying method 40 10%
コーティング膜が単層又は複数層から形成することができる。通常、手術直後は感染率も高いので、２以上の層から形成し、抗菌剤または抗菌薬の単位時間あたりの溶出量を表層に近いほど高くするのが好ましい。その溶出量は通常コーティング膜の消失速度に依存するので、コーティング槽が複数層からなり、各層の抗菌剤または抗菌薬の単位時間あたりの溶出量を各層の抗菌剤または抗生物質の含有量又は各層の消失速度により調整する。 The coating film can be formed from a single layer or a plurality of layers. Usually, since the infection rate is high immediately after the operation, it is preferable to form two or more layers, and to increase the elution amount per unit time of the antibacterial agent or antibacterial agent closer to the surface layer. Since the amount of dissolution usually depends on the disappearance rate of the coating film, the coating tank consists of multiple layers, and the amount of dissolution per unit time of the antibacterial agent or antibacterial agent in each layer is the content of the antibacterial agent or antibiotic in each layer or each layer. Adjust according to the disappearance rate of.
本発明の消失性コーティング膜は生体インプラントのコバルト−クロム（Ｃｏ−Ｃｒ）及びチタン（Ｔｉ）−合金インプラント上に直接形成されても良いが、従来通り、合金インプラント上に形成される非消失性のリン酸カルシウムコーティング上に本発明の消失性コーティングを形成するのがよい。 The vanishing coating film of the present invention may be formed directly on the cobalt-chromium (Co-Cr) and titanium (Ti) -alloy implants of biological implants, but is conventionally non-destructible formed on the alloy implants. The vanishing coating of the present invention may be formed on the calcium phosphate coating.
本発明の消失性コーティングは感染症の防止のためであるから、コーティング位置は関節包との接合部およびその周辺であるのが適当である。 Since the disappearing coating of the present invention is for the prevention of infection, it is appropriate that the coating position is at the joint with the joint capsule and its periphery.
本発明のコーティング膜に抗菌剤又は抗生剤を担持させる方法は、薬剤の種類によって異なる。即ち、バンコマイシンなどの抗生剤の場合は、コーティング層を先に形成させた後に溶かした抗生剤を含浸させる方法を採用する。ヒノキチオールなどの天然系抗菌剤やベンザルコニウムなどの有機系抗菌剤など液体系の抗菌剤の場合も同様の方法が有効であるが、シランカップリングなどの結合剤で固定して使用することができる。一方、銀イオン、銅イオン、亜鉛イオンなどの金属イオンの抗菌作用を利用する無機系抗菌剤の場合はこれらを予めリン酸カルシウム系材料に担持させ、上記各種コーティング法を採用して担持させることができる。なお、抗菌剤と抗生剤とを両方担持させることができる。 The method for supporting the antibacterial agent or antibiotic on the coating film of the present invention varies depending on the type of the drug. That is, in the case of an antibiotic such as vancomycin, a method of impregnating the dissolved antibiotic after the coating layer is formed first is employed. The same method is effective in the case of liquid antibacterial agents such as natural antibacterial agents such as hinokitiol and organic antibacterial agents such as benzalkonium, but it may be used by fixing with a binder such as silane coupling. it can. On the other hand, in the case of inorganic antibacterial agents that utilize the antibacterial action of metal ions such as silver ions, copper ions, and zinc ions, these can be supported in advance on a calcium phosphate-based material and can be supported using the various coating methods described above. . In addition, both an antibacterial agent and an antibiotic can be carried.
ＨＡ９７％、酸化銀３％を混合し、フレーム溶射法にてチタン基板上に平均２０μｍの溶射被膜を形成させた。その結晶度は１０％であった。図１は本発明の機能を示す概念図である。チタン基板上に形成されたコーティング膜は体液中で次第に溶解し、消失する。溶出に伴い、銀イオンを液中に放出する。
１）銀イオン溶出試験
３７℃のリン酸緩衝生理食塩水、牛血清で溶出試験を行った所、２４時間でそれぞれ５２０ｐｐｂ、４０００ｐｐｂの溶出を示した
２）抗菌性能試験
JIS Z 2801に従って、大腸菌、黄色ブドウ球菌に対する抗菌性能を評価した所、それぞれ抗菌活性値４．１及び５．０という高い値を示した
３）被膜の消失
３７℃の生理食塩水に浸漬した所、約６ヶ月で被膜が溶解、消失した
HA97% and silver oxide 3% were mixed, and a sprayed coating with an average of 20 μm was formed on the titanium substrate by flame spraying. Its crystallinity was 10%. FIG. 1 is a conceptual diagram showing functions of the present invention. The coating film formed on the titanium substrate gradually dissolves and disappears in the body fluid. Along with the elution, silver ions are released into the liquid.
1) Silver ion elution test When elution test was performed with 37 ° C phosphate buffered saline and bovine serum, 520 ppb and 4000 ppb elution were observed in 24 hours, respectively. 2) Antibacterial performance test
According to JIS Z 2801, the antibacterial performance against Escherichia coli and Staphylococcus aureus was evaluated, and the antibacterial activity values were 4.1 and 5.0, respectively. 3) Disappearance of the film Placed in 37 ° C physiological saline The film dissolved and disappeared in about 6 months
実施例１で製作した被膜を６５０℃、３時間熱処理した。結晶度は６０％であった。
３７℃のリン酸緩衝生理食塩水、牛血清を用いて銀イオン溶出試験を行った所、２４時間でそれぞれ１９ｐｐｂ、１８００ｐｐｂの溶出を示した。結晶度を変化させてやることによって、溶出特性はこのように大きく変化する。
The coating produced in Example 1 was heat treated at 650 ° C. for 3 hours. The crystallinity was 60%.
When silver ion elution test was performed using 37 ° C. phosphate buffered saline and bovine serum, elution of 19 ppb and 1800 ppb were observed in 24 hours, respectively. By changing the crystallinity, the elution characteristics change greatly in this way.
ＨＡ９７％、酸化銀３％を混合し、スパッタリング法にてチタン基板上に平均２μｍの被膜を形成させた。その結晶度は１０％であった。
１）銀イオン溶出試験
３７℃の牛血清中で溶出試験を行った所、２４時間で２８０ｐｐｂの溶出を示した。
２）抗菌性能試験
JIS Z 2801に従って、大腸菌、黄色ブドウ球菌に対する抗菌性能を評価した所、抗菌活性値はそれぞれ２．４と２．８であった。
（注記）JIS Z 2801では抗菌活性値２．０以上を抗菌活性ありと判定する。
３）被膜の消失
３７℃の生理食塩水に浸漬した所、約３週間で被膜が溶解、消失した。
HA 97% and silver oxide 3% were mixed, and an average film thickness of 2 μm was formed on the titanium substrate by sputtering. Its crystallinity was 10%.
1) Silver ion elution test When the elution test was performed in 37 ° C bovine serum, elution of 280 ppb was shown in 24 hours.
2) Antibacterial performance test
According to JIS Z 2801, antibacterial activity against Escherichia coli and Staphylococcus aureus was evaluated. The antibacterial activity values were 2.4 and 2.8, respectively.
(Note) In JIS Z 2801, an antibacterial activity value of 2.0 or more is judged to have antibacterial activity.
3) Disappearance of film The film dissolved and disappeared in about 3 weeks when immersed in physiological saline at 37 ° C.
酸化銀３％とα−ＴＣＰ９７％とを混合し、フレーム溶射法にてチタン基板上に平均４０μｍの被膜を形成させた。その結晶度は１００％であった。
１）銀イオン溶出試験
３７℃の牛血清中で溶出試験を行った所、２４時間で１２０００ｐｐｂの溶出を示した。
２）抗菌性能試験
JIS Z 2801に従って、大腸菌、黄色ブドウ球菌に対する抗菌性能を評価した所、抗菌活性値は６．４と６．２という高い値を示した。
Silver oxide 3% and α-TCP 97% were mixed, and an average film thickness of 40 μm was formed on the titanium substrate by flame spraying. Its crystallinity was 100%.
1) Silver ion elution test When an elution test was performed in 37 ° C bovine serum, 12000 ppb elution was shown in 24 hours.
2) Antibacterial performance test
When antibacterial performance against E. coli and Staphylococcus aureus was evaluated according to JIS Z 2801, the antibacterial activity values were as high as 6.4 and 6.2.
銀１．８５％を含有するリン酸カルシウム系ガラス粉末をフレーム法にてチタン基板上に平均４０μｍの溶射被膜を形成させた。コーティング層は非晶質であった。
１）銀イオン溶出試験
３７℃の牛血清中で溶出試験を行った所、２４時間で２５００ｐｐｂの溶出を示した
２）抗菌性能試験
JIS Z 2801に従って、大腸菌、黄色ブドウ球菌に対する抗菌性能を評価した所、抗菌活性値は７．８と４．９という高い値を示した
A sprayed coating with an average of 40 μm was formed on a titanium substrate by a frame method using calcium phosphate glass powder containing 1.85% silver. The coating layer was amorphous.
1) Silver ion dissolution test When dissolution test was performed in 37 ° C bovine serum, it showed 2500ppb dissolution in 24 hours 2) Antibacterial performance test
According to JIS Z 2801, antibacterial activity against Escherichia coli and Staphylococcus aureus was evaluated, and the antibacterial activity value was as high as 7.8 and 4.9.
（人工股関節への適用）
図２Ａは正常股関節、図２Ｂは変形性股関節症を患った股関節および図２Ｃは人工股関節を適用した股関節の間接部を示す断面図で、人工股関節として図３にシェル（Ａ）とステム（Ｂ）との斜視図を示す（出典 図説整形外科診断治療講座（第１５巻 人工関節・バイオマテリアル）（室田景久等））。
シェル（Ａ）はＴｉ合金からなり、その上方の半球面部全面には結晶性ＨＡコーティング膜が施されており、そのシェル（Ａ）のコーティング膜の下方辺縁部には実施例１と同様にして消失性コーティング膜が形成されている。他方、ステム（Ｂ）のネック下には結晶性ＨＡコーティング膜が形成され、そのコーティング膜の上方辺縁部には実施例１と同様にして消失性コーティング膜が形成されている。
これら消失性コーティング膜は間接包の周囲の細菌の侵入がしやすい部分に形成されているので、間接包からの細菌の感染を防止することができる。したがって、インプラント手術後の感染症の発生を有効に防止することができる。
(Application to artificial hip joints)
2A is a normal hip joint, FIG. 2B is a hip joint suffering from osteoarthritis, and FIG. 2C is a cross-sectional view showing an indirect portion of a hip joint to which an artificial hip joint is applied. FIG. 3 shows a shell (A) and a stem (B ) (Source: Illustrated Orthopedic Diagnosis and Treatment Course (Volume 15 Artificial Joints / Biomaterials) (Keihisa Murota, etc.)).
The shell (A) is made of a Ti alloy, and a crystalline HA coating film is applied to the entire surface of the hemispherical surface above the shell (A), and the lower edge of the coating film of the shell (A) is the same as in the first embodiment. An extinct coating film is formed. On the other hand, a crystalline HA coating film is formed under the neck of the stem (B), and a vanishing coating film is formed on the upper edge of the coating film in the same manner as in the first embodiment.
Since these disappearing coating films are formed on the part around the indirect package where bacteria can easily enter, it is possible to prevent bacterial infection from the indirect package. Therefore, it is possible to effectively prevent the occurrence of infection after implant surgery.
本発明は、生体インプラントである人工骨、内固定具及び人工関節に適用され、消失性コーティング膜の結晶度、組成により抗菌剤、抗生剤の放出速度、それらと膜厚により放出期間を調整することができるので、生体インプラントの感染症予防に最適である。特に、コーティング膜の消失性を利用することができるので、無機系抗菌剤を有効に利用できる利点がある。 The present invention is applied to artificial bones, internal fixation devices, and artificial joints that are biological implants, and the release period is adjusted by the release rate of antibacterial and antibiotic agents according to the crystallinity and composition of the evanescent coating film, and the film thickness. Therefore, it is optimal for the prevention of infectious diseases of biological implants. In particular, since the disappearance of the coating film can be used, there is an advantage that the inorganic antibacterial agent can be used effectively.
Ａ：人工股関節シェル部、Ｂ：人工股関節ステム部 A: artificial hip joint shell, B: artificial hip stem
Claims (8)
Priority Applications (7)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2006252933A JP5069888B2 (en) | 2006-09-19 | 2006-09-19 | Biological implant |
| CN200780033447.7A CN101511399B (en) | 2006-09-08 | 2007-08-20 | Bioimplant |
| PCT/JP2007/066119 WO2008029612A1 (en) | 2006-09-08 | 2007-08-20 | Bioimplant |
| US12/440,430 US10004604B2 (en) | 2006-09-08 | 2007-08-20 | Bioimplant for artifical joint with evanescent coating film |
| US16/017,309 US10610614B2 (en) | 2006-09-08 | 2018-06-25 | Bioimplant with evanescent coating film |
| US16/823,175 US11278642B2 (en) | 2006-09-08 | 2020-03-18 | Bioimplant with evanescent coating film |
| US17/673,651 US11998659B2 (en) | 2006-09-08 | 2022-02-16 | Bioimplant with evanescent coating film |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2006252933A JP5069888B2 (en) | 2006-09-19 | 2006-09-19 | Biological implant |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2008073098A true JP2008073098A (en) | 2008-04-03 |
| JP5069888B2 JP5069888B2 (en) | 2012-11-07 |
Family
ID=39345794
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2006252933A Active JP5069888B2 (en) | 2006-09-08 | 2006-09-19 | Biological implant |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP5069888B2 (en) |
Cited By (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2012023510A1 (en) | 2010-08-19 | 2012-02-23 | 国立大学法人佐賀大学 | Biological implant |
| JP2013518653A (en) * | 2010-02-04 | 2013-05-23 | フィンズブリー・（デヴェロップメント）・リミテッド | Prosthesis |
| WO2013114947A1 (en) | 2012-02-03 | 2013-08-08 | 国立大学法人佐賀大学 | Bioimplant |
| JP2014050610A (en) * | 2012-09-07 | 2014-03-20 | Advance Co Ltd | Dental implant and method for producing dental implant |
| JP2014097160A (en) * | 2012-11-14 | 2014-05-29 | Univ Of Tokyo | A composite manufacturing method, calcium phosphate thin film, composite, and hydroxyapatite thin film |
| JP2017060889A (en) * | 2008-02-29 | 2017-03-30 | スミス アンド ネフュー インコーポレイテッド | Gradient coating for biomedical applications |
| KR101756428B1 (en) * | 2015-11-23 | 2017-07-11 | 기초과학연구원 | Emission control method of pH-responsive nitric oxide using calcium phosphate |
| US9839720B2 (en) | 2008-02-29 | 2017-12-12 | Smith & Nephew, Inc. | Coating and coating method |
| US10814039B2 (en) | 2012-02-03 | 2020-10-27 | Kyocera Corporation | Bioimplant with antibacterial coating and method of making same |
| WO2020250911A1 (en) * | 2019-06-12 | 2020-12-17 | 日本特殊陶業株式会社 | Biocompatible member |
| WO2021153795A1 (en) | 2020-01-31 | 2021-08-05 | 京セラ株式会社 | Spinal implant and method for manufacturing spinal implant |
| JPWO2021240798A1 (en) * | 2020-05-29 | 2021-12-02 | ||
| JPWO2021240797A1 (en) * | 2020-05-29 | 2021-12-02 | ||
| US11576997B2 (en) | 2018-03-05 | 2023-02-14 | Chubu University Educational Foundation | Iodine-loaded bone repair material and method for producing the same |
| US11998659B2 (en) | 2006-09-08 | 2024-06-04 | Kyocera Corporation | Bioimplant with evanescent coating film |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6113993A (en) * | 1998-10-28 | 2000-09-05 | Battelle Memorial Institute | Method of coating a substrate with a calcium phosphate compound |
| JP2005097052A (en) * | 2003-09-25 | 2005-04-14 | Japan Science & Technology Agency | Hydroxyapatite with large surface area and its manufacturing method |
| JP2005297435A (en) * | 2004-04-14 | 2005-10-27 | Crystal Coat:Kk | Multilayered film, composite material, implant and composite material manufacturing method |
| JP2006151729A (en) * | 2004-11-26 | 2006-06-15 | Shikoku Instrumentation Co Ltd | Composite material introduced with calcium phosphate layer and its manufacturing method |
-
2006
- 2006-09-19 JP JP2006252933A patent/JP5069888B2/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6113993A (en) * | 1998-10-28 | 2000-09-05 | Battelle Memorial Institute | Method of coating a substrate with a calcium phosphate compound |
| JP2005097052A (en) * | 2003-09-25 | 2005-04-14 | Japan Science & Technology Agency | Hydroxyapatite with large surface area and its manufacturing method |
| JP2005297435A (en) * | 2004-04-14 | 2005-10-27 | Crystal Coat:Kk | Multilayered film, composite material, implant and composite material manufacturing method |
| JP2006151729A (en) * | 2004-11-26 | 2006-06-15 | Shikoku Instrumentation Co Ltd | Composite material introduced with calcium phosphate layer and its manufacturing method |
Cited By (26)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US11998659B2 (en) | 2006-09-08 | 2024-06-04 | Kyocera Corporation | Bioimplant with evanescent coating film |
| JP2017060889A (en) * | 2008-02-29 | 2017-03-30 | スミス アンド ネフュー インコーポレイテッド | Gradient coating for biomedical applications |
| JP2019150648A (en) * | 2008-02-29 | 2019-09-12 | スミス アンド ネフュー インコーポレイテッド | Gradient coating for biomedical applications |
| US9839720B2 (en) | 2008-02-29 | 2017-12-12 | Smith & Nephew, Inc. | Coating and coating method |
| KR101764605B1 (en) * | 2010-02-04 | 2017-08-03 | 핀즈버리 (디벨롭먼트) 리미티드 | Prosthesis |
| JP2016025884A (en) * | 2010-02-04 | 2016-02-12 | フィンズブリー・（デヴェロップメント）・リミテッド | Processing for producing prosthesis |
| KR101819885B1 (en) | 2010-02-04 | 2018-01-19 | 핀즈버리 (디벨롭먼트) 리미티드 | Prosthesis |
| JP2013518653A (en) * | 2010-02-04 | 2013-05-23 | フィンズブリー・（デヴェロップメント）・リミテッド | Prosthesis |
| WO2012023510A1 (en) | 2010-08-19 | 2012-02-23 | 国立大学法人佐賀大学 | Biological implant |
| JP2017127744A (en) * | 2012-02-03 | 2017-07-27 | 国立大学法人佐賀大学 | Biological implant |
| US11577006B2 (en) | 2012-02-03 | 2023-02-14 | Kyocera Corporation | Bioimplant |
| WO2013114947A1 (en) | 2012-02-03 | 2013-08-08 | 国立大学法人佐賀大学 | Bioimplant |
| US10814039B2 (en) | 2012-02-03 | 2020-10-27 | Kyocera Corporation | Bioimplant with antibacterial coating and method of making same |
| JP2014050610A (en) * | 2012-09-07 | 2014-03-20 | Advance Co Ltd | Dental implant and method for producing dental implant |
| JP2014097160A (en) * | 2012-11-14 | 2014-05-29 | Univ Of Tokyo | A composite manufacturing method, calcium phosphate thin film, composite, and hydroxyapatite thin film |
| US10301332B2 (en) | 2015-11-23 | 2019-05-28 | Institute For Basic Science | Method of selectively releasing nitric oxide depending on change in pH using calcium phosphate |
| KR101756428B1 (en) * | 2015-11-23 | 2017-07-11 | 기초과학연구원 | Emission control method of pH-responsive nitric oxide using calcium phosphate |
| US11576997B2 (en) | 2018-03-05 | 2023-02-14 | Chubu University Educational Foundation | Iodine-loaded bone repair material and method for producing the same |
| WO2020250911A1 (en) * | 2019-06-12 | 2020-12-17 | 日本特殊陶業株式会社 | Biocompatible member |
| WO2021153795A1 (en) | 2020-01-31 | 2021-08-05 | 京セラ株式会社 | Spinal implant and method for manufacturing spinal implant |
| JPWO2021240798A1 (en) * | 2020-05-29 | 2021-12-02 | ||
| WO2021240798A1 (en) * | 2020-05-29 | 2021-12-02 | 京セラ株式会社 | Stem for artificial joint |
| JPWO2021240797A1 (en) * | 2020-05-29 | 2021-12-02 | ||
| WO2021240797A1 (en) * | 2020-05-29 | 2021-12-02 | 京セラ株式会社 | Stem for artificial joint |
| JP7499326B2 (en) | 2020-05-29 | 2024-06-13 | 京セラ株式会社 | Artificial joint stems |
| JP7499325B2 (en) | 2020-05-29 | 2024-06-13 | 京セラ株式会社 | Artificial joint stems |
Also Published As
| Publication number | Publication date |
|---|---|
| JP5069888B2 (en) | 2012-11-07 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP5069888B2 (en) | Biological implant | |
| Buck et al. | Surface modification strategies to improve the osseointegration of poly (etheretherketone) and its composites | |
| JP6596200B2 (en) | Gradient coating for biomedical applications | |
| Graziani et al. | Ion-substituted calcium phosphate coatings deposited by plasma-assisted techniques: A review | |
| Duan et al. | Surface modifications of bone implants through wet chemistry | |
| US7132015B2 (en) | Materials for dental and biomedical application | |
| Lin et al. | Suppl 1-M4: A review paper on biomimetic calcium phosphate coatings | |
| WO2008029612A1 (en) | Bioimplant | |
| US20100286790A1 (en) | Implant and method for coating an implant | |
| JP2004358249A (en) | Strontium-substituted apatite coating | |
| JP6289708B2 (en) | Biological implant | |
| CN110234365A (en) | The method of medical implant and coating medical implant | |
| Shimizu et al. | Bioactive effects of strontium loading on micro/nano surface Ti6Al4V components fabricated by selective laser melting | |
| US11998659B2 (en) | Bioimplant with evanescent coating film | |
| Mohapatra et al. | Ceramic coatings for wound healing applications | |
| CN105749345B (en) | For be easy to remove implant from separating layer | |
| Navarro et al. | Biomimetic mineralization of ceramics and glasses | |
| Victoria Cabanas | Bioceramic coatings for medical implants | |
| JP3166352B2 (en) | Implant components | |
| Bernstein et al. | Thin Degradable Coatings for Optimization of Osseointegration Associated with Simultaneous Infection Prophylaxis | |
| Jirofti et al. | Review on Hydroxyapatite-Based Coatings as Antibiotic Delivery System on Bone Graft Substitution for Controlling Infection in Orthopedic Surgery | |
| Tran et al. | Aaqil Rifai2 and Kate Fox2, 3 1Interface Science and Materials Engineering Group, Queensland University of Technology, Kelvin Grove, QLD, Australia, 2School of Engineering, RMIT University, Melbourne, Vic, Australia, 3Centre for Additive Manufacturing, RMIT University | |
| Rafik Rafik | Optimization of a thermochemical process and antibacterial properties for 3D printed prostheses of titanium | |
| DeYoung et al. | Implant Materials and Surface Coating | |
| Epinette et al. | Histology and Fate of Bioactive Coatings |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20090709 |
|
| RD03 | Notification of appointment of power of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7423 Effective date: 20090709 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20120515 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20120703 |
|
| TRDD | Decision of grant or rejection written | ||
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20120724 |
|
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20120820 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20150824 Year of fee payment: 3 |
|
| R150 | Certificate of patent or registration of utility model |
Ref document number: 5069888 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| S111 | Request for change of ownership or part of ownership |
Free format text: JAPANESE INTERMEDIATE CODE: R313115 |
|
| R350 | Written notification of registration of transfer |
Free format text: JAPANESE INTERMEDIATE CODE: R350 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |